Processing set and methods for processing and treating a biological fluid

ABSTRACT

Apparatus, systems and methods are disclosed for treating a biological fluid with light. A container of biological fluid is introduced into a fluid treatment chamber where it is contacted with light provided by one or more light sources in proximity to the fluid treatment chamber. A drawer for holding containers of biological fluid introduces the containers into the chamber. Containers for holding the biological fluid are marked by the apparatus to indicate the status of the treatment.

This is a divisional application of U.S. patent application Ser. No.09/325,599, filed Jun. 3, 1999 now U.S. Pat. No. 7,025,877.

The present invention generally relates to a systems and methods forprocessing and treating biological fluids, such as blood and bloodcomponents. More particularly, the present invention relates to improvedapparatus, systems and methods for the light treatment of a biologicalfluid that contains a light activated photochemical agent, for thepurpose of inactivating pathogens that may be present in such biologicalfluid.

Apparatus, methods and systems for treating biological fluids, such asblood and blood components, with light are well known. For example, U.S.Pat. No. 4,952,812, incorporated by reference herein, discloses anapparatus for treating unwanted white blood cells in plateletconcentrate with ultraviolet radiation to limit the white cells' abilityto trigger an immune reaction in a patient. To treat containers ofplatelet concentrate, the containers are placed on a slidable drawerthat is introduced into a housing between facing arrays of lamps forirradiation from both sides of the container. During irradiation, thedrawer (or a portion of the drawer) may be pivoted in a rocking motionto agitate the platelet concentrate.

U.S. Pat. No. 5,557,098, also incorporated by reference herein,discloses a system and apparatus for treating a biological fluid withlight for the purpose of inactivating pathogens that may be present inthe biological fluid. A slidable drawer is used to position thecontainers of biological fluid between facing arrays of light emittingdiodes. Extended flaps on the containers, located outside the lightfield, are automatically punched to indicate different stages of thelight treatment.

U.S. patent application Ser. No. 08/121,820, filed Sep. 15, 1993, whichis also incorporated by reference herein, discloses apparatus andmethods for treating a container of a blood product between two facingarrays of light. The container includes a light sensitive tape whichchanges color when exposed to ultraviolet light, thereby indicating whenthe treatment process is complete.

Still other apparatus and systems for treating biological fluid aredisclosed in U.S. Pat. No. 5,709,991, and U.S. patent application Ser.No. 09/081,168, filed May 18, 1998, both of which are incorporated byreference herein.

While the prior art apparatus, systems and methods have generally workedsatisfactorily, work continues to develop new and improved apparatus,systems and methods that provide, for example, improved reliability,greater flexibility and efficiency, improved ease of use andserviceability, as well as enhanced tracking, record keeping and thelike.

SUMMARY OF THE INVENTION

In one aspect, the present invention is embodied in a disposableprocessing set for treating a biological fluid that includes a firstportion including a container for containing the biological fluid duringtreatment, a second portion including a container for receiving thebiological fluid after treatment, and tubing connecting the containersand defining an openable flow path therebetween. The processing setincludes a holder for temporarily holding the second portion separatefrom the first portion.

In another aspect, the present invention is embodied in a method forproviding a substantially pathogen-free biological fluid that includesproviding a biological fluid in a collection container wherein thecollection container includes a length of tubing extending therefrom.The tubing includes a sealed end and defines an openable flow pathbetween the collection container and the sealed end. The method furtherincludes providing a disposable fluid processing set comprising at leasta first container integrally connected to a second container and alength of tubing extending from the second container, wherein the tubingincludes a sealed end and an openable flow path between the firstcontainer and the sealed end.

The method further includes joining the collection container tubing andthe first container tubing in a sterile manner and establishing fluidcommunication between the collection container and the first container.The biological fluid is then transferred from the collection containerto the first container. A photochemical agent is also combined with thebiological fluid. The method includes providing a light source capableof providing a light sufficient to activate the photochemical agent, andtreating the biological fluid in the first container by contacting thebiological fluid with light from the light source. The status of thetreatment of the fluid in the first container is indicated on the secondcontainer to which the biological fluid is afterward transferred.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of an apparatus for treating a biologicalfluid with light, embodying the present invention;

FIG. 2 is a perspective view of the apparatus of FIG. 1 showing themodular components of the apparatus separated;

FIG. 3 is a perspective view of the apparatus of FIG. 1 with the frontaccess door open;

FIG. 4 is a perspective view of the apparatus of FIG. 1 with front, topand side panels removed;

FIG. 5 is a partially exploded view of the apparatus of FIG. 1;

FIG. 6 is a perspective view of a light drawer with socket panel open;

FIG. 6A is an exploded view of the light drawer of FIG. 6.

FIG. 7 is a perspective view of a fluid container carrying tray;

FIG. 8 is a perspective view of fluid carrying drawer with tray removed;

FIG. 8A is a partial side view of the drawer tilt knob and assembly ofthe fluid carrying drawer;

FIG. 8B is a modified partial side view of the drawer tilt knob andassembly of the fluid carrying drawer;

FIG. 9 is another perspective view, from the underside, of the fluidcarrying drawer without fluid container carrying tray;

FIG. 10 is a front view of the fluid carrying drawer with fluid carryingtray removed showing side to side oscillation of the tray;

FIG. 11 is a perspective view of container marker assembly;

FIG. 11A is another perspective view, from the underside, of thecontainer marker assembly;

FIG. 12 is an enlarged perspective view of an individual marking unit ofthe container marker assembly;

FIG. 13 is a perspective view of stacked apparatus embodying the presentinvention;

FIG. 14 is a block diagram of the control system of the apparatusembodying the present invention;

FIG. 14A is a perspective view of a light sensing device which may beused with the apparatus of FIG. 1;

FIG. 15 is a plan view of a disposable fluid processing set embodyingthe present invention;

FIG. 16 is a plan view of another disposable fluid processing setembodying the present invention;

FIG. 17 is a plan view of a disposable fluid processing set embodyingthe present invention in position for attachment with containers of acollected biological fluid;

FIG. 18 is a perspective view of a part of the disposable fluidprocessing set embodying the present invention that includes at leastone container disposed within a holder;

FIG. 18A is a perspective view of an alternative embodiment of theholder in a closed position with containers disposed therein;

FIG. 18B is a perspective view of the holder of FIG. 18A in an openposition but without container(s);

FIG. 18C is a perspective view of another alternative embodiment of aholder in an open position;

FIG. 18D is a perspective view of another alternative embodiment of aholder with frame portions separated;

FIG. 19 is a flow chart showing the start-up phase of the control systemfor the present invention;

FIG. 20A is a flow chart showing the pretreatment phase of the controlsystem for the present invention;

FIG. 20B is a continuation of the flow chart of FIG. 20A;

FIG. 21 is a flow chart showing the treatment phase of the controlsystem for the present invention;

FIG. 22 is a flow chart showing the operator initiated instrumentsettings functions of the control system for the present invention; and

FIG. 23 is a flow chart showing the diagnostic functions of the controlsystem for the present invention.

DETAILED DESCRIPTION

For purposes of illustration, the various aspects of the presentinvention will be described, in large part, in connection with theirpreferred embodiments. However, it should be recognized that theapparatus, systems and methods embodying the different aspects of thepresent invention are not limited to the specific details describedherein.

An apparatus for treating a biological fluid is generally shown in FIGS.1–14 and is referred to herein generally as light box 10. Light box 10may be used for treating a variety of materials for a variety ofpurposes.

Light box 10 is particularly useful in the treatment of biologicalfluids. As used herein, biological fluid refers to any fluid that isfound in or that may be introduced into the body including, but notlimited to, blood and blood products. As used herein “blood product”refers to whole blood or a component of whole blood such as red bloodcells, white blood cells, platelets, plasma or a combination of one ormore of such components that have been separated from whole blood.

One specific, non-limiting use of light box 10 is in the treatment of ablood product that has been combined with a photochemical agent foractivation when subjected to light. Such photochemical agents are used,for example, in the inactivation of viruses, bacteria, white blood cellsand other contaminants (collectively referred to herein as “pathogens”).In pathogen inactivation applications, the activated agent inactivatespathogens that may be present in a blood product.

Typically, the biological fluid to be treated is introduced into a fluidtreatment chamber within light box 10 in flexible, plastic,sterilizable, translucent, biologically compatible containers. Inaccordance with aspects of the present invention, the containers may beintegrally connected to other containers and plastic tubing useful inthe processing of the biological fluid both before and after thetreatment provided by light box 10. Examples of the disposableprocessing set and its components are shown in FIGS. 15–18. The lightbox, the disposable processing set and the methods of using them aredescribed in more detail below.

a. Light Box

As shown in FIG. 1, light box 10 includes a housing 12 defined by toppanel 14, bottom panel 16, front and rear panels 17, and side panels 18.Housing 12 is supported by feet 13 attached to bottom panel 16 (FIG. 4).In a preferred embodiment, feet 13 are rubber or other elastomericmounts. Side panels 18 may include handles 22 for grasping andtransporting light box 10. An openable or removable door 24 in sidepanel 18 allows for access to the interior of light box 10 and, morespecifically, the electronic components of light box 10, which aredescribed in more detail below. Door 24 may be opened or removed byturning fasteners 25.

For convenience and efficiency, it is preferred that light box 10 befairly compact. In one, non-limiting example, light box 10 may beapproximately 100 cm wide, 20–40 cm deep and between approximately 30–40cm high. A compact instrument allows, for example, for placement of agreater number of instruments per treatment center and/or may allow twoor more instruments to be stacked on top of each other (as shown in FIG.13), resulting in greater throughput of biological fluid per horizontalarea or space (i.e. bench space, shelf space).

Light box 10 may include a control module 26 and a fluid treatmentmodule 28. As described in more detail below, control module 26 mayinclude and/or house the command and control elements for the treatmentof biological fluid. Fluid treatment module 28 houses the elements andcomponents where fluid processing takes place.

Control module 26 and fluid treatment module 28 may be contained in thesame housing but in a preferred embodiment, as shown in FIG. 2, they arereadily separable modules. Control module 26 and fluid treatment module28 are electrically and physically connected when light box 10 is inuse, but may be separated as shown in FIG. 2. In one embodiment, controlmodule 26 and fluid treatment module 28 are held together, in part, bydraw pin 30 (FIG. 4) which holds together interfitting parts of themodules. Control module 26 and fluid treatment module 28 may beseparated by removing draw pin 30 and turning of fasteners 31 shown inFIG. 4. Fasteners 31 may be accessed by removing door 24 (shown inFIG. 1) in side panel 18. Of course, other means of connecting andreadily separating control and fluid treatment modules may be used,including, mating clips and slots on the facing panels of the control 26and fluid treatment module 28.

Providing light box 10 in two readily separable modules 26 and 28 allowsfor easier access to the control and fluid treatment modules 26 and 28and, generally, provides for easier serviceability of light box 10. Forexample, if off-site service is required for control module 26 only,that module can be removed without requiring removal and transport ofthe entire light box 10.

As shown in FIGS. 1 and 2, the exterior of control module 26 includes acontrol panel 32 located in the front of light box 10. Control panel 32includes, a display screen 37 such as, but not limited to, an LCDdisplay for providing graphical, textual and alphanumerical informationto the operator regarding the treatment process. Also included withincontrol panel 32 of control module 26 is a key pad 39 to allow operatorcontrol over the process and/or for data entry by the operator.Additional means of data entry are provided by bar code reader 41 which,when not in use, rests in slot 43. A trough 45 may be provided for thecoiled cable of bar code reader 41. Control panel may also include theon/off switch 35 for light box 10.

The interior components of control module 26 are generally shown in FIG.4. Control module 26 will typically include a programmablemicroprocessor for operation of light box 10 including centralprocessing unit 27 and memory devices such as random access memory (RAM)and EPROMS for the system program storage and non-volatile memory forback-up data storage. Control module 26 may further include an isolationtransformer 29 for converting an AC input voltage to a DC control systemvoltage and for maintaining leakage current within acceptable limits formedical devices. Other components within control module 26 may includepower supply 167, input/output board 33 and a power inlet module 34,filtered pass through 34 b for use with an external light intensitysensing device and filtered output pass through 34 a.

Control module 26 may be adapted for connection to external componentssuch as a printer 500 (FIG. 14) through parallel and/or serial ports34C, or to a central computer 502 (FIG. 14) that is connected to severallight boxes and/or other medical devices. The central computer canreceive data from the several instruments, allowing the operator at atreatment center to retrieve information regarding the severalprocedures. As will be appreciated by one of ordinary skill, controlmodule 26 may also include other components such as additional printedcircuit boards shown in FIG. 14

Turning now to the fluid treatment module 28, as shown in FIGS. 1–3,fluid treatment module 28 includes front door 36 which when opened,allows for introduction and removal of the biological fluid into a fluidtreatment chamber, as described in more detail below. The front panel 17of fluid treatment module 28 may also be opened to allow for fulleraccess to the interior of fluid treatment module. As shown in FIG. 3,panel 17 may include fasteners 17 a which, when turned, allow frontpanel 17 to be opened or removed.

FIGS. 4–5 generally show the interior of fluid treatment module 28 withat least top panel 14 and front panel 17 removed. As best seen in FIG.5, fluid treatment module 28 includes an interior framework 38 thatdefines, in part, a fluid treatment chamber 40 and light chambers 42 and44 for housing light sources (described in more detail below). Theframework 38 may typically be constructed of any sturdy material whichwill allow light box 10 to support one or more additional light boxes asgenerally shown in FIG. 13. A preferred material is aluminum and, inparticular, Aluminum 6061 hardened to T-6.

Returning to FIG. 5, the light chambers 42 and 44 are located above andbelow fluid treatment chamber 40 to provide two-sided illumination ofthe biological fluid. Of course, it will be appreciated that light box10 may include a single light chamber, placed in close proximity tofluid treatment chamber or two or more light chambers disposed around afluid treatment chamber in other than “top and bottom” positions.

As shown in FIGS. 3–5, fluid treatment chamber 40 is adapted to receivefluid carrying drawer 50. Light chambers 42 and 44 are adapted toreceive light drawers 60 and 70. Fluid treatment module 28 may furtherinclude a container marker assembly 74 shown, for example, in FIG. 5.Marker assembly 74 may carry one or more markers 76 a–76 d for markingcontainers, before and/or after treatment, as will be discussed in moredetail below.

Turning more specifically to a description of fluid carrying drawer 50,as shown in FIG. 13, fluid carrying drawer 50 allows for introduction ofbiological fluid into fluid treatment chamber 40. Fluid carrying drawer50 may be moveable, either manually or automatically, into and out offluid treatment chamber 40. Where manual movement of fluid carryingdrawer 50 is required, drawer 40 may include handle 80. In oneembodiment, movement of fluid carrying drawer 50 is facilitated byslides 82 on either or both sides of drawer 50, which are disposedwithin rails 86 of framework 38, as best seen in FIGS. 8, 9 and 13.Alternatively, fluid carrying drawer 50 may include rollers or otherdevices which allow for movement of drawer 50 into and out of fluidtreatment chamber 40.

For ease of loading and unloading containers of biological fluid, fluidcarrying drawer 50 preferably includes a pivot mount that permits thedrawer to be tilted downwardly when fully withdrawn. The ability to tiltdrawer 50 downwardly may be particularly useful for loading containersof fluid in the upper light boxes where two or more light boxes arestacked on top of each other, as shown in FIG. 13. In one embodiment,fluid carrying drawer 50 may be hingedly attached to framework 38 sothat when fluid carrying drawer 50 is fully opened and is outside ofhousing 12, front edge of drawer 50 may be tilted downwardly at, forexample, a 45° angle. To allow tilting of fluid carrying drawer, lightbox 10 may include spring loaded tilt knob 83 which, when pulled,releases fluid carrying drawer 50 and allows it to be tilted in themanner described above. More specifically, as shown in FIG. 8A, tiltknob 83 is connected to rod 82 a which is attached to slide 82 (FIG. 9).The end of rod 82 a is coupled to pivot member 83 a which is connectedto ring 83 b attached to drawer 50. Rod 82 a further includes a spring82 c and spring stops 82 d. When the end of rod 82 a is coupled to pivotmember 83 a, movement of ring 83 b is prevented (as shown in FIG. 8A).However, when knob 83 is pulled, (as shown in FIG. 8B) rod 82 a isuncoupled from pivot member 83 a, allowing ring to rotate relative topivot member 83 a and, thereby, allowing drawer 50 to be tilteddownwardly, as shown in FIG. 13.

As shown in FIGS. 8–9, fluid carrying drawer 50 is generally open andincludes a central cavity 88 to allow for placement of a containercarrying tray 90 shown in FIG. 7. Container carrying tray 90 may beintegral with fluid carrying drawer 50, although, a removablenon-integrated tray 90 may be preferable for easier container loadingand/or tray cleaning.

During treatment of the biological fluid, it may be desirable that thefluid within fluid carrying drawer 50 be continuously or periodicallyagitated to provide mixing of the biological fluid and ensure thatsubstantially all of the biological fluid is sufficiently and uniformlyexposed to light and/or any photochemical agent. Accordingly, fluidcarrying drawer 50 may be attached to means for agitating the biologicalfluid.

As shown in FIGS. 9 and 10, fluid carrying drawer 50 may include anagitation assembly that, for example, provides side-to side oscillationof tray 90. Agitation assembly may include a pair of fixed lower rails95 b that extend front to back within light chamber. Upper rails 95 aare attached to the lower rails by pivotally attached link arms 93 a and93 b. The link arms allow side-to-side motion of the upper rails 95 a.To provide oscillation, an electrical motor 92 is attached to lower rail95 b. Motor 92 rotates a cam 97 a. Cam 97 a may be an L-shaped crank orbracket attached to roller 97. Roller 97 is captured between parallelwalls 97 b depending from upper rail 95 a. As crank 97 a causes roller97 to orbit around the motor 92 axis, roller slides fore and aft and upand down between walls 97 b, imparting side-to-side motion of upper rail95 a.

Light box 10 may include one or more light sources, preferably disposedabove and below fluid treatment chamber 50. For ease of serviceability,such as lamp replacement, it is preferable that the light source(s) bereadily accessible. As used herein, “readily accessible” means thataccess to the light source can be quickly and easily had without the useof, for example, a screwdriver or other tools. For example, in oneembodiment, it may be desirable that the light source be eitherpartially or completely removable from the housing 12 and/or fluidtreatment module 28. The light source(s) may be accessible through anyone of the front, side, top or bottom panels. In one embodiment, thelight sources are housed in light drawers 60 and 70. As shown in FIG. 5,when front panel 17 and/or door 36 are removed or opened, light drawersmay be moveable (or even completely removable) into and out of fluidtreatment module 28. Light drawers 60 and 70 may include slides 99 (FIG.6) attached to the bottom surface of drawers 60 and 70. Slides 99 restand move on brackets 96 and slide mounting blocks 98 of framework 38 asshown in FIG. 5. Light drawers 60 and 70 may also include handles 84 forgrasping during insertion and removal.

As shown in FIG. 6, light drawer 60 and/or 70 may be divided into two ormore chambers 101 and 103 separated by dividing wall 102. Dividing wall102 minimizes light from one light chamber of radiating into the otherlight chamber. This ensures that the light emitted from each lamp orlamp array and contacting the biological fluid is substantiallyconstant. In addition, each of the lamp arrays within light chambers 101and 103, may be independently monitored and controlled from controlmodule 26. Thus, when one array of lamps is turned off, the other arrayof lamps may remain on. As described in more detail below, this may beparticularly useful where two or more containers of biological fluidrequiring different levels of treatment are being treated.

Each of light chambers 101 and 103 of light drawer 60 or 70 is generallydefined by four side walls 105 a–d and a bottom wall 107. Walls 105 a–dand 107 may be made of or coated with a reflective material to maximizethe amount of light delivered to the biological fluid. In one specificembodiment, where the light source provides light in the ultraviolet A(UVA) range, walls 105 a–d and 107 may be made of a highly reflectivealuminum to provide substantial reflection of UVA light. Such a materialis sold under the name 1500 G-2 and is available from ALANOD ofEnnepetal, Germany.

The light sources suitable for use in the present invention may includeany light source that is capable of providing light of a particularwavelength and intensity for treating a particular biological fluid. Forexample, light sources capable of providing white light, red light,infrared, ultraviolet A and/or B light may be used. Light drawers 60 and70 may include a single lamp or an array of multiple lamps 100. In oneembodiment, light source may include standard fluorescent lamps or bulbscapable of providing light of a wavelength in the UVA (ultraviolet A)range. Such lamps may be obtained from Sagyo Denkai of Japan under theproduct code BL352. Light drawers 60 and 70 further include fans 109 forcooling lamps 100 and, more specifically, ends of lamps 100 at or nearthe lamp filaments.

As shown in FIG. 6, the ends of lamps 100 are inserted into sockets 104housed on socket panel 106. Socket panel may also serve as a printedcircuit board. Socket panel 106 may be hinged and openable to allow foreasy access to lamps 100, easy insertion and removal of lamps 100, andin general, easier serviceability of light drawers 60 and 70.

As shown in FIG. 5, a portion of fluid treatment chamber 40 and, forthat matter, fluid carrying drawer 50, are separated from light drawers60 and 70 by glass plates 110. As shown in FIG. 5, upper glass plate 110rests on framework 38 and is, generally, held in place by clamps 112 and114. A lower glass plate 110 separating a portion of fluid carryingdrawer 50 from lower light drawer 70 may also be included. Glass plates110 are substantially translucent to light of the wavelengths used forthe treatment of biological fluid. Preferably, glass plates 110 may alsofilter unwanted light. Alternatively, a separate filter may be providedfor placement between the light source and the fluid treatment chamber40. In one specific embodiment, where treatment of a biological fluidwith UVA light is desired, glass plate 110 may be substantiallytranslucent to ultraviolet light within the range to 320–400 nm, but nottranslucent to light of a wavelength of less than about 320 nm. Suchglass plates are commercially available from Schott Glass of Yonkers,N.Y. under the product designation B-270.

As set forth above, fluid treatment module 28 further includes markerassembly 74. Marker assembly 74 may include one or more markers 76 a–76d for marking containers within fluid treatment chamber. One or moremarkers 76 may be provided to mark containers at different stages of thetreatment. Markers 76 a–d may be punches for punching holes into aportion of the container such as the container flap as described in U.S.Pat. No. 5,557,098, which is incorporated by reference. Alternatively,and more preferably, markers may be stampers for stamping designatedportions of a container with ink. Such markers are commerciallyavailable from Trodat of Wels, Austria under the product name Printy4911.

As shown in FIG. 11, marker assembly 74 may include a plurality ofmarkers 76 a–d for marking a plurality of containers during differentstages of the light treatment. Markers 76 a–d may be attached to abracket 78 which includes a slide 114. Slide 114 is suspended from andmovable within track 116 which is attached to the interior framework 38of light box 10. Thus the entire assembly 74 can be withdrawn from fluidtreatment module 28 for reinking, replacement of markers 76 or forgeneral servicing as shown in FIG. 5.

As shown in FIG. 12, each individual marker unit includes a marker drivemotor 120 that moves markers 76 up and down through gear 122, gear 124,lead screw 128, lead nut 126, bracket 130 and spring 132. Movement ofgears 122 and 124 actuates movement of lead screw 128 and causesdownward and/or upward movement of lead nut 126, bracket 130 andconsequently marker 76.

Fluid treatment module 28 includes blower 134 which provides air flowinto fluid treatment chamber 40 and fluid containers and thus, providesfor temperature control of fluid treatment chamber 40 (FIG. 5). Blower134 receives ambient air through an opening in bottom wall 16 locatedbelow blower 134. In addition to providing air to fluid treatmentchamber 50, air from blower 134 may also pass through opening 136 offluid treatment module 28 and a perforation or opening 136 a in controlmodule 26, as seen, for example in FIGS. 2 and 4.

Returning to the fluid treatment module 28 and more specifically fluidcarrying drawer 50, as shown in FIGS. 5 and 13, fluid carrying drawer 50may include a tray 90 for holding one or more containers of biologicalfluid. Tray 90, shown in FIG. 7, may be placed within the cavity 88 ofthe fluid carrying drawer 50 (FIG. 8). In one embodiment, tray 90 may bemade of a molded plastic material. Where the biological fluid is treatedfrom two sides, the molded plastic material should be sufficientlytranslucent to the light provided by the lamps 100. Suitable materialsfor tray 90 include acrylic polymers such as polymethyl methacrylate(PMMA) or members of the polyolefin family such as methylpentenecopolymer. Such materials are available from many sources including CYROIndustries of Rockaway, N.J. under the product name ACRYLITE® OP4 orfrom Mitsui Plastics of White Plains, N.Y. under the name TPX.

Where one or more containers are to be treated, tray 90 may be dividedinto a first portion 180 and a second portion 182 separated by dividingwall 184. As shown in FIG. 7, tray 90 may include retaining tabs 186 forplacing a slit or other aperture of a biological fluid container 206over tab 186 to limit movement of the container within tray 90 andensure that the container is substantially within the field of lightprovided by the light source. The volume of tray 90 should be sufficientto hold at least the entire volume of biological fluid contained withinthe containers so as to minimize the risk that, in the event ofcontainer leakage, liquid will overflow and contact the electrical andmechanical components of light box 10, even during agitation.

Where the biological container is part of an integrated fluid processingset, tray 90 may be compartmentalized to provide separate compartmentsfor the container undergoing treatment on the one hand, and theremainder or a portion of the remainder of the disposable processingset, on the other hand. As shown for example, in FIG. 7, first portion180 and second portion 182 each include a first compartment 188 andsecond compartment 190 separated by discontinuous wall 192. Firstcompartment 188 may hold a container of biological fluid 206 and thesecond compartment may hold the remaining components of the fluidprocessing set. A slot in the wall 192 accommodates the tubing thatconnects container 206 with the remainder of the disposable processingset. Tray 90 or second compartment 190 of tray may further includecontainer retaining tabs or pegs 193 to assist in holding the containersin the second compartment in place and limiting movement of suchcontainers within tray 90.

When the tray 90 with disposable processing set is introduced into fluidtreatment chamber 50, container 206 within a first compartment 188 ispositioned substantially within the field of light provided by the lightsource. The remainder of the disposable processing set and/or containerswithin a second compartment 190 are aligned substantially with markerassembly 74 as shown in FIGS. 4 and 5. Thus, the status of the treatmentmay be indicated on the other containers of the processing set withinthe second compartment 190 by markers 76 a–d.

Light box 10 may include sensors for detecting different conditionsduring the pretreatment and treatment process. The sensors relay signalsto the microprocessor of the light box 10 which is housed within controlmodule 26. As shown for example in FIG. 14, sensors (e.g., 404, 430)send signals through the sensor input/output board 33 which translatesthe signal into a format that is understandable by microprocessor 160.The computer alerts the operator, either by an audible alarm or amessage on the display screen 37. The operator may, in response to thealarm or message, take action through keypad 39. Alternatively, inresponse to certain alarm conditions, the control system may bepreprogrammed to automatically take action, such as terminate treatment,if necessary.

For example, light box 10 may include internal light intensity sensors404 for measuring the intensity of light provided by the lamps 100 tofluid treatment chamber 50. In the event that the light intensityprovided by lamps 100 is insufficient for the desired treatment, sensor404 sends a signal through input/output board 170 (FIG. 14) tomicroprocessor 160 as described above.

In one embodiment, light intensity sensors 404 may be located within thelight chambers 101 and 103 of light drawers 60 and 70 (FIG. 6). In oneembodiment, light drawer 60 and/or 70 include a light intensity sensorsubassembly 402 on the underside of drawer 60 and/or 70. As shown inFIG. 6 a, subassembly 402 includes two or more sensors 404 attachedthereon and placed within sensor windows 406 located in the bottom wall107 of drawers 60 and/or 70. Sensor windows 406 allow light from lamps100 to pass through and contact sensors 404. Sensors 404 may include orbe used with one or more filters to filter out unwanted light. Morespecifically, where light box 10 is used to activate a photochemicalagent, it may be desirable that the filters used in association withsensors 404 have a maximum sensitivity in the wavelength range thatsubstantially matches the wavelength range within which the particularphotochemical agent is most effectively activated (i.e., the “actioncurve”). This allows sensor 404 to detect the effectiveness ofphotochemical activation. Such sensors are available from Texas AdvancedOptoelectronics Solutions under the product code TSL230B. Filters areavailable from a variety of sources such as Schott Technical Glass ofDuryea, Pa.

A fluid carrying drawer sensor 144 may be included for monitoring theposition of fluid carrying drawer within fluid treatment chamber 40.Fluid carrying drawer positioning sensor 144 ensures that the drawer 50is in a fully closed position and therefore, that containers ofbiological fluid are substantially within the field of light provided bylamps 100. If the drawer is not in a fully closed position, sensor 144sends a signal to the microprocessor, alerting the operator andpreventing treatment from proceeding.

Light box 10 may further include temperature sensors 145 for eitherdirectly or indirectly monitoring and measuring the temperature withinfluid treatment chamber 40. Temperature sensor may be disposed withinthe fluid treatment chamber 40 or, as shown in FIGS. 4 and 5, may bedisposed on the exterior of light box 10 to measure the ambienttemperature of the outside environment. For example, ambient temperaturesensor 145 may be located anywhere on the surface of light box 10. Inone embodiment, as shown in FIGS. 1 and 2, ambient temperature sensor145 is placed at or near control module 26. Ambient temperature sensor145 provides an indication of the air temperature being delivered tofluid treatment chamber by blower 134. In the event that the temperaturefalls outside of a predetermined temperature range, the ambienttemperature sensor sends a signal to the microprocessor as generallydescribed above, which alerts the operator that the temperature isapproaching or has exceeded its limit. Accordingly, the operator and/orinstrument may take further action.

Additional sensors may be provided, including a sensor for monitoringthe agitation provided by the agitation assembly. Sensor 430 may beattached to marker subassembly 74, as shown in FIG. 11A, and measuresmovement of the agitation assembly described above. In one embodiment,sensor 430 may include an infrared source such as, but not limited to alight emitting diode (LED) or laser that contacts a selected reflectiveportion of the agitation assembly. If sensor 430 does not detectreflection or does not detect reflection at the predetermined frequency,it signals the microprocessor accordingly.

Light box 10 may also include a sensor 440 to detect whether the frontdoor of the light box is closed during treatment. Door sensor may be amagnetic switch which detects contact between door 36 and magnetic plate441 shown in FIG. 3. Also, plunger switch 36 a (FIG. 4) is pressed whendoor 36 is closed. If door 36 is open, plunger switch 36 a serves as anelectrical cut off. If, the door is open, the system will not permit thetreatment to proceed.

Light box 10 may also include sensors 450 for determining whethercontainers are in position for marking by markers 76. As shown in FIG.11A, sensors 450 may be attached to markers 76 and may include opticalreceivers aligned with light emitting diodes (LED) (not shown) typicallylocated below fluid carrying tray 90. The labels of containers placedwithin the second compartment 190 of tray 90 prevent optical receiver450 from receiving the LED signal, indicating the presence of acontainer. Conversely, if sensor 450 receives the signal, this indicatesthat no container is present and the marker will not be activated. Inaddition, each marker 76 a–d may include a microswitch (shown as 470 inFIG. 14) to detect whether movement of the marker has occurred and toprevent mechanical failure or damage the parts that make up the marker.

In addition, a portable and attachable light intensity sensing,verification and calibration device or radiometer 460 may be provided toverify light intensity provided by light box 10 and for calibration oflight box 10. Radiometer 460 may be adapted for placement within fluidtreatment chamber 40 for measuring the energy dose delivered to thebiological fluid. More specifically, radiometer 460 may be adapted forplacement within the fluid container carrying tray 90. In oneembodiment, radiometer 460 may be adapted for placement within acompartment of tray 90 such as first compartment 188 of tray 90.

As shown in FIG. 14A, radiometer 460 may include a support 465 having atop surface 467 and a bottom surface 468. Support 465 is typically aprinted circuit board. One or more sensors 469 are electrically andphysically connected to support 465.

It is known that a light source may not always uniformly emit light. Forexample, depending on the age of the lamp, the intensity of lightemitted from one part of the lamp may not be the same as the intensityemitted from another part of the lamp. Accordingly, in a preferredembodiment, as shown in FIG. 14A, radiometer 460 may include a pluralityof sensors spaced across the top and/or bottom surface(s) to receivelight from different points on one or more lamps. Also, sensors 469 maybe placed on one side of support 465, but preferably are placed on boththe top surface 467 and the bottom surface 468. Top and bottom placementof sensors 469 is particularly preferred where radiometer 460 is used tomeasure light provided by two facing light sources, such as in one ofthe embodiments of light box 10.

An electrical cord (not shown) is attached to radiometer 460 forelectrical connection to light box 10 and, for example, port 461 (FIG.5). This allows radiometer 460 to transmit data to the computer-basedcontrol system of light box 10, which system provides information to theoperator and/or automatically takes action based on the transmitteddata. Radiometer 460 may also include a slit 472 for placement over tab186 in tray 90 of light box 10.

Sensors 469 may typically be photodiodes capable of detecting light ofselected wavelengths. Sensors 469 may also include or be used withfilters to filter out unwanted light as substantially described above.

When used in connection with light box 10, it is preferred that thedimensions of radiometer 460 be substantially equivalent to thedimensions of the fluid-filled containers used with light box 10.Accordingly, it is preferred that the light sensing area of radiometer460 have a height, a width and a thickness substantially equal to suchfilled containers. A radiometer with dimensions substantially equal tothe fluid-filled container provides a reliable approximation of theenergy being delivered to the fluid and of the effectiveness of thetreatment.

As set forth above, radiometer 460 may be used for light intensityverification by, for example, the operator and for calibration of lightbox 10 generally and more specifically, of internal sensors 404. Inaccordance with the method of using radiometer 460 for light intensityverification, the operator may place radiometer 460 in first compartment188 of tray 90. Cord may be pressed into strain relief tabs 474 withinlight box 10 (FIG. 8). The fluid carrying drawer 50 is inserted intofluid treatment chamber 40 and door 36 is closed. Lamps 100 are turnedon and the light delivered is measured by sensors 469. Specifically, thelight measured by sensors 469 is processed by the system'smicroprocessor to provide a reading of the energy being provided to thefluid treatment chamber 40. The operator can monitor the output of lamps100 and determine any diminishment in the lamp output by comparing thereading to a pre-set acceptable energy dose range. In addition, thereadings provided by sensors 469 are also compared to the readingsprovided by sensors 404 to detect any diminished sensing capability ofsensors 404.

Thus, for example if the energy dose measured by radiometer 460 issubstantially equal to the energy dose detected by sensors 404, but isoutside the pre-set dose range, this may be an indication that theoutput of lamps 100 has diminished and that lamps 100 may have to bereplaced. Alternatively, if the energy dose as measured by radiometer460 is substantially equal to the expected pre-set dose of theinstrument, but both are different from the energy dose as measured bysensors 404, this may be an indication that sensing capability ofsensors 404 has diminished. Finally, if the dose as measured by sensors404 is substantially equal to the expected pre-set dose, but differentthan the energy dose as measured by radiometer 460, this may indicatethat the sensing capability of radiometer 460 has diminished. Radiometermay also be used to calibrate light box 10. Radiometer 460 itself may becalibrated against a standard (e.g. a standard from the NationalInstitute for Standards and Technology or NIST).

Of course, it will be appreciated that radiometer 460 may have utilityin other applications and is not limited to use in the apparatus ormethods of the present invention. Indeed, radiometer 460 may be usedwhenever light is to be measured over an extended surface area.

The components of the fluid treatment module 28 including the agitatorassembly, the light sources, the blower, the marker subassembly arepowered by power supplies as shown in FIG. 14. (In FIG. 14, the letter“n” represents the number of electrical or mechanical components such assensors, lamps, ballasts etc.). For example, power supplies (ballasts)166 power lamps 100 and are controlled and supplied by relay board andisolation transformer 29. Shaker motor 92 is powered through relay boardand isolation transformer 29. Additional power supply 168 supplies powerfor the blower 134, light drawer fans 109, and drive motors 120 formarkers 76 a–d and door lock 480. Preferably, the power supply forpowering these components may be approximately 24 volts DC. Power supply167 may supply +5, +12, −12 volts DC to, for example, computer board160.

Finally, light box 10 includes a programmable computer software-basedcontrol system to control the operation of light box. The control systemis generally and diagrammatically depicted in FIGS. 19–23 and isdescribed in greater detail in connection with the description of themethod of processing and treating a biological fluid which follows thedescription of the disposable proceessing set provided below.

b. Disposable Processing Set

Disposable processing sets useful with light box 10 are shown in FIGS.15–18. Typically, the disposable processing set will include two or moreplastic containers integrally connected by plastic tubing. At least oneof the containers should be suitable for holding the biological fluidduring light treatment. The other container should be suitable forstorage of the biological fluid after treatment. As described in moredetail below, the disposable processing set may be joined withcontainers of biological fluid, and the fluid may be transferred tocontainers of the disposable processing set.

One embodiment of a disposable fluid processing set 200 is shown in FIG.15. Processing set 200 includes a container 202, a container 206, acontainer 210 and a container 214. The containers may be integrallyinterconnected with tubing segments as generally shown and described indetail below. The sizes and internal volumes of containers 202, 206, 210and 214 may vary depending on the biological fluid being processed. In anon-limiting example, container 202 may be capable of holdingapproximately 15–30 ml of fluid, containers 206 and 210 approximately1000 ml and container 214 between approximately 1000–1500 ml. Of course,other desirable sizes and volumes may be used and are within the scopeof the present invention.

Where the disposable processing set is used in or as part of a pathogeninactivation treatment, container 202 may include, for example, aphotochemical agent which is mixed with the biological fluid. Examplesof such photochemical agents include psoralen compounds described inU.S. Pat. No. 5,709,991 and compounds from the family of phenothiazinedyes such as, but not limited to, methylene blue. Container 202 may bemade of any material suitable for holding such photochemical agents. Onesuch material may be a blend of ethylene polypropylene, polyamide and ablock copolymer of ethylene and butylene with terminal blocks ofpolystyrene. Containers made of such material are available from BaxterHealthcare Corporation under the name PL2411. Container 202 includes atubing segment 203 extending therefrom and having a sealed end 204. Asecond tubing 205 extending from container 202 is integrally connectedto container 206. In another embodiment, the photochemical agent may becontained or predisposed within container 206, thereby eliminating theneed for a separate container 202 for holding the photochemical agent.In still another embodiment, the photochemical agent may be combinedwith the biological fluid prior to joinder to the disposable processingset. For example, the photochemical agent may be included in a container201 used to hold the biological fluid collected from a donor (FIG. 17).

Container 206 is preferably a container suitable for holding thebiological fluid during light treatment. Accordingly, it is desirablethat container 206 be made of a clear, durable, thermoplastic materialthat is translucent to light of the selected wavelength and sterilizableby known forms of sterilization including steam sterilization, gamma andelectron beam radiation. For example, where the blood product to betreated includes blood platelets or blood plasma and the treatment is tobe with light in the UVA range, container is made of a material that issubstantially translucent to UVA light and remains stable aftersterilization. Such materials may include polyvinyl chloride, but morepreferably, may be blends of thermoplastic polymers and copolymers,including general purpose polymers, elastomers and the like. One suchmaterial includes the block copolymer described above which includes acentral block of ethylene and butylene and terminal blocks ofpolystyrene. Block copolymers of the type described above are availablefrom the Shell Chemical Company under the name KRATON. The blockcopolymer may be blended with other polymers such as ultra low densitypolyethylene (ULDPE) and ethylene vinyl acetate (EVA). Containers madeof the blended material are available from Baxter Healthcare Corporationof Deerfield, Ill. under the name PL-2410. Other thermoplastic materialsmay also be suitable for container 206, including materials includingKRATON, EVA, and polypropylene. A container made from such material isalso available from Baxter Healthcare Corporation under the name PL-732.Still other suitable materials for container 206 include fluoropolymerssuch as polytetrafluoroethylene (PTFE), PFA or copolymers including suchfluoropolymers.

Container 206 further includes a slit 207 which, as described above, maybe placed over retaining tab 186 in tray 90. Container 206 includes atubing segment 208 which may be integrally connected to a container 210.

In the pathogen inactivation of biological fluid, container 210 may, forexample, include an adsorbent material 211 for removing excessphotochemical agent or the byproducts of the photoactivation process.The adsorbent material may be contained in a semi-permeable pouch,preferably affixed to the container walls or portions thereof within theinterior chamber of container 210. The interior chamber of container 210has a volume sufficient to hold the biological fluid from container 206.Such a container and the adsorbent material are disclosed in more detailin copending patent application entitled “Plastic Containers HavingInner Pouches and Methods for Making Such Containers” which is beingfiled simultaneously herewith in the names of Mahmood Mohiuddin, GeorgeD. Cimino and Derek J. Hei, and is incorporated by reference in itsentirety. Materials such as those used in the PL-2410 and PL-732containers described above are suitable for use in container 210.

Container 210 may also include a time-sensitive tape 209. Tape 209changes color with time, thus informing the operator if the biologicalfluid has contacted the adsorbent material for a sufficient period oftime. Container 210 may be integrally connected by tubing segment 211 toanother container 214 which may be suitable for storage of thebiological fluid. As shown in FIG. 15, the portion of tubing segment 211that communicates with the interior of container 210 may include afilter 211a to capture loose particles of adsorbent, if any.

Container 214 may include and/or be capable of receiving a label 216which may carry bar codes 222 or other indicia which provide informationabout the biological fluid. For example, bar codes 222 may identify thedonor, the product, the lot number of the biological fluid, expirationdate and the like. Container 214 may include additional bar codes orindicia 224 which are used to provide information regarding the statusor progress of the fluid treatment (described in more detail below).Container 214 may also include a slit 226 and/or apertures 228, 230 forplacement over corresponding pegs (193) on tray 90. Materials such asthose described above are suitable for use in container 214. Container214 may also include sampling pouches 214 a and access ports 214 b toallow for fluid access during later transfusion, as will be recoginzedby those of ordinary skill.

In an alternative embodiment, disposable processing set may include asingle container for housing the adsorbent material of container 210 andfor storing the biological fluid, thereby combining the functions ofcontainer 210 and 214 described above.

The disposable processing set 200 described herein may further includefrangible members 230 (a–c) disposed within tubing segments as shown inFIG. 15. Frangible members 230 are broken at the appropriate time toestablish fluid communication between the containers of the processingset 200. Such frangible connectors are described in detail in U.S. Pat.No. 4,294,297 which is incorporated by reference herein. Tubing segmentsof disposable processing set 200 may further include indicators 234 aand 234 b on the tubing to indicate proper positioning of the disposableprocessing set within the tray 90 (as will be described more detailbelow) and/or to serve as indicators of where tubing is to be severedand sealed. In one embodiment, indicators 234 may be plastic ringsdisposed around tubing segments. Of course, other tubing indicatingmeans may be used.

Another embodiment of a fluid processing set is shown in FIG. 16. InFIG. 16, disposable processing set 240 also includes a container 242which carries a photochemical agent, a container 244 which holds thebiological fluid during light treatment, a container 246 which includesan adsorbent material for removing excess photochemical agent and/or thebyproducts of the photoactivation process, and a container 248 suitablefor storage of the biological fluid. Container 248 is adapted to receivelabel 249 with bar codes or other indicia and may include additionalindicia 251 including, for example, additional bar codes assubstantially described above.

In contrast to the container 210 of the earlier described embodiment,container 246 is a flow through device which includes adsorbent material212 but does not include a chamber for holding the biological fluid forany significant period of time. Such flow through devices are describedin International Publication No. WO 96/40857 which is incorporated byreference herein. Disposable processing set 240 may further include anair reservoir 256 and air sink 258. Air reservoir 256 provides air tohelp expel biological fluid from container 244 and air sink 258 receivesexcess air expelled from storage container 248 after processing. Airreservoir 256 and air sink 258 may be made of any suitable biocompatiblematerial, including the materials described above. Likewise, thecontainers of disposable processing set 240 may also be made from thematerials generally described above. Preferably, container 256 issubstantially impermeable to air.

As in the embodiment of FIG. 15, the containers of disposable processingset 240 shown in FIG. 16 may be integrally interconnected by tubingsegments 243, 245 and 247. Tubing segments may further include frangiblemembers 249 (ac) for opening fluid communication between the containers.

Disposable processing set 200 (or 240) is typically provided to the userin a sealed package in a manner that is easy for the user to unpack anduse. For example, upon opening the package, it is preferred that thecontainer to be used first in the fluid processing be located near thetop of the package. For example, in the processing set 200 shown in FIG.15, container 202 would be located near the top of the package, followedby container 206, followed by the remainder of the disposable processingset that includes containers 210 and 214. In addition, if disposableprocessing set includes container 202, (or 242 in the embodiment of FIG.16) at least such container should include a separate and additionallight impermeable overwrap to protect the contents (i.e. thephotochemical agent) from exposure to light which could result inpremature activation of the photochemical agent. In one embodiment, thelight impermeable overwrap may be permanently sealed to the outer wallsof container 202.

In a preferred embodiment, containers 210 and 214 may be containedwithin or held together by a holder. Holder may be any device such as aclamp that holds together containers 210 and 214. The holder may beintegral with the disposable processing set or may be providedseparately.

More preferably, holder 260, shown in FIGS. 17–18, may be a receptacleor other shell-like holding device. In one embodiment, holder 260 mayinclude a bottom wall 262 which separates the containers 210 and 214from container 206. In a preferred embodiment, holder 260 may havesidewalls 262 and 264, a back wall 268 and includes a substantially openfront portion as shown in FIGS. 17–18. In addition, bottom wall 262 mayinclude a slot 263 to accommodate tubing that connects containers ofdisposable processing set 200. Holder 260 may also include additionalside openings 265 (shown, for example, in FIG. 17) for holding tubingsegments of container 202 prior to unpackaging of the disposableprocessing set. Holder 260 may be made of any suitable material such asbut not limited to plastic or cardboard. Preferably, holder 260 is madeof a moldable plastic material that may be sterilizable and impactresistant.

Alternative embodiments of holder 260 are shown in FIGS. 18A–18D. Asshown in FIGS. 18A–18C, holder may include two frame or partial frameportions 600 and 602. Frame portions 600 and 602 may be joined andinclude hinge 604 as shown in FIGS. 18B and 18C. Alternatively, framemembers 600 and 602 may be completely separable as shown in FIG. 18D.Frame portions 600 and 602 include means for securing together the frameportions such as mating slots 605 and pins or lugs 606 as shown. Holder260 shown in FIGS. 18A–18D includes a central opening 608 to allow thelabel of a container placed within holder 260 to be exposed to theoutside environment to allow scanning by, for example, a bar code readerand/or marking by markers 76 as described below.

In one embodiment, container 210 is placed in the front portion ofholder 260, such that a label to be applied to the container 210 andother indicia on the container itself are exposed to the outsideenvironment through the open portion of holder 260 as shown in FIG. 17.For purposes of illustration, in FIGS. 17–18, label is shown as appliedto container 214. In one embodiment container 214 may not include labelat the time of use and a label may be transferred to container 214 froma container of biological fluid. Alternatively, container 214 mayinclude a label and an additional label may be transferred from acontainer of biological fluid. In any event, container 214 may be foldedin half (or tri-folded) with container 210 (also folded) placed behindcontainer 214. In addition, folded container 214 may be lightly spotwelded at its ends to keep the container folded and improvehandleability of the container. The weld should be sufficiently strongto keep container 214 in a folded position, but not so strong that undueforce applied by the user would be required to disconnect the weldedends. Spot welded ends of container 210 should release when tuggedgently by the user.

c. Methods of Processing and Treating Fluid

The method of processing fluid using disposable processing set 200 (or240) and treating a biological fluid with light in, for example, lightbox 10 will now be described. Although the following description will beprovided in the context of processing the biological fluid forsubsequent inactivation of pathogens in the biological fluid, it shouldbe understood that many of the steps described below may also be carriedout in other fluid processing and treating methods that do not involvepathogen inactivation. The following description will be provided usingthe disposable processing set of FIG. 15 as an example, although it willbe understood that the description may also apply to other processingsets, such as the set of FIG. 16.

In accordance with the method of processing a biological fluid such asblood using the processing set 200, a container of collected blood orbiological fluid is provided. Although the method of collection isbeyond the scope of the present application, representative methods ofcollecting blood products include the automated and manual centrifugalprocessing, separation and collection of blood products, membraneseparation of blood products and the like. One example of a centrifugalblood processing system is the AMICUS® Separator sold by BaxterHealthcare Corporation.

Regardless of the collection method, containers of the collected bloodproduct will typically bear a label that includes informationidentifying the donor, the blood product and lot numbers. Mosttypically, such information is presented in the form of one or more barcodes on the label which can be scanned and read by bar code reader,such as bar code reader 41 of light box 10. Such labels may be removableand transferable to container 214 of the disposable processing set 200.

Typically, the collection container will include a tubing segmentextending therefrom. Accordingly, tubing from the collection container201 and tubing segment 203 from the disposable processing set 200 arebrought together and joined in a sterile manner, as shown generally inFIG. 17. A device that is useful for the the sterile joinder of tubingportions is available from Terumo Corporation of Japan and sold underthe name Terumo SCD. This device heat seals two opposing tubing portionsin a sterile manner. The heat from the heat sealing kills any bacteriafrom the outside environment that may enter or reside in the tubingsegments, thereby preserving the sterility of the entire processing set.Of course, any method and apparatus for joining two tubing segmentswhile maintaining sterility may be used.

Once tubing segments have been joined, frangible member 230 a is brokento provide an open flow path from the collection container 201 to thecontainer 206 (FIG. 15). Photochemical agent from container 202 is alsoallowed to flow into container 206. After fluid transfer to container206, tubing segment may be severed and sealed and the portion of thedisposable processing set that included container 202 and the collectioncontainer(s) 201 are discarded. Indicator 234 a provides a referencepoint as to where the tubing is to be severed. It is preferable that theindicator be placed as close as possible to the container 206 so thatmost of the biological fluid is retained within container 206 where itis most likely to be mixed and treated.

Before or after placement of the disposable processing set in tray 90,operator may scan the label and other container indicia with bar codereader 41. Bar codes 222 on the main container label 216 or thecontainer itself provide the instrument with information regarding thebiological fluid to be treated. Based on the data, the light treatinginstrument or operator prescribes the light dosage and then calculatesthe duration of the treatment.

Container 206 of disposable processing set 200 is typically placed infirst compartment of tray 90. Slit 207 in container 206 is placed overretaining tab 186 in first compartment 188 and holder 260 withcontainers placed therein are placed within the second compartment 190of tray 90. Slits and/or apertures in container 216 are likewise placedover retaining tabs or pegs 193 in second compartment 190. Tubingconnecting container 206 with container 210 (and/or 214) may be pressedinto the slot in wall 192. It is preferable that the tubing bepositioned parrallel to the direction of the side-to-side oscillationprovided by the agitator assembly described above. This further ensuresthat any fluid within tubing segment 208 is also mixed. Indicator 234 bnot only serves as a reference point for severance of the tubing butalso serves as a reference point for container placement by ensuringthat substantially the entire container and biological fluid therein iswithin the field of light. The indicator has a diameter greater than thewidth of the slot.

Once the containers are in their respective compartments of tray 90,fluid carrying drawer 50 is closed. As set forth above, plunger switch36 a (FIG. 4) is pressed when door 36 is closed. If door 36 is open,plunger switch 36 a serves as an electrical cut off. If, the door isopen, the system will not permit the treatment to proceed.

Light box 10 includes a programmable computer software-based controlsystem to control the operation of light box 10. The control system isgenerally and diagrammatically depicted in FIGS. 19–23. As shown inFIGS. 19–23, the system tests, monitors and controls various aspects ofthe light box 10 and treatment operation such as the start up, containerloading, container treatment and container unloading stages of the lightbox operation. The control system allows the operator to take action oradvises the operator of the treatment status through either analphanumeric or a graphical user interface displayed on screen 37. Thevarious functions may be initiated by the operator through control panelor automatically by the control system itself.

For example as shown in FIG. 19, after the operator has turned on theinstrument (step 300), the control system will initiate a series ofsteps including loading the software 301, initializing the software 302,and displaying the graphical user interface screen and menu 304. Theoperator may then select from the series of available functionsincluding the treatment function 306 or general user function 308.Alternatively, the operator may choose to exit the system 312.Diagnostic checks 310 may also be selected and performed, typically by aservice technician.

If the treatment function 306 is selected, the control system, throughthe programmed software will automatically determine if treatment isappropriate and more particularly, if the light box 10 is prepared fortreatment as shown in FIG. 20A. Thus, for example, if the system detectsa failure in the light source, or a failure in one of the sensors orother equipment, treatment will not be enabled and would not proceeduntil the condition is remedied. If treatment is enabled however, thesystem will prompt the operator to input his or her unique identifier314 and then request the input of container (i.e. biological fluid)information 316. Container information may be input manually or byscanning bar codes 222 on, for example, container 214 shown in FIG. 15.If treatment is appropriate, the system proceeds to the next function orphase as generally shown in FIG. 20B.

As shown in FIG. 20B, the control system displays additional options forthe operator to select. For example, the operator may proceed totreatment of the container, request treatment of a second container orcancel the operation entirely as shown in step 320. If “Bag 2” option isselected, the operator is again requested to input container information322 and the system will repeat the steps generally described above. Iftreatment on a single container is to be performed, the operator selectsthe treat function 324 which is generally shown in FIG. 20B anddescribed in more detail below.

After containers have been placed into tray 90, to commence treatmentthe system activates the light source(s) 100, shaker motor 92 and fansas shown in step 328 of FIG. 21. The instrument may display, forverification by the operator, information regarding the fluid to betreated and the treatment process generally. For example, in oneembodiment, the instrument may display, the predetermined target dose ofenergy to be applied to containers, the selected treatment time and arunning value of the dosage percent being applied to the biologicalfluid during the treatment as shown in 330. Treatment will continueunless terminated by the operator or automatically terminated by theinstrument in response to an alarm condition.

In one embodiment, container may be marked by markers 76 at thebeginning of treatment and after treatment is completed. The marks madeby marker 76 obliterate or otherwise masks the bar code, making itunreadable. Thus, a container with two masked bar codes 224 indicatesthat treatment has been successfully completed. On the other hand, ifonly one of the bar codes 224 has been masked, this serves as anindication that treatment was not successfully completed and thecontainer may have to be discarded. Masking of bar codes 224 by markers76 also ensures that a treated container will not be treated again.

During treatment, the system performs an energy calculation 332 which iscomputed by multiplying the light intensity sensor readings bypreselected calibration factors, averaging the readings across thesensors in the same chamber and plane and adding the reading receivedfor planes in the same chamber. The control system further verifies thetreatment status 334. If treatment is completed, the system willautomatically turn off lamps 100 as shown in 336.

The system may automatically update information on the lamp life asshown in 337 and update container records 338. Control system maycontinue to power shaker motor 92 until terminated. The results may betransmitted to a central computer 502 (FIG. 14). After treatment, thesystem will prompt the operator to unload containers 342 and may promptthe user to perform another treatment, if desired, as shown in 325 inFIG. 20B. The process may be repeated as generally described above.

Treatment time and energy dosage will vary depending on the biologicalfluid to be treated. For example, the treatment time may be at least oneminute but may also be less than one minute. Where light box 10 is usedfor the pathogen inactivation of biological fluid, the treatment maytypically be anywhere between 1–30 minutes. For example, for thepathogen inactivation of blood platelets, treatment is typically between1–10 minutes, but more typically approximately 3–4 minutes. For thepathogen inactivation of blood plasma, treatment may also preferably beapproximately 3–4 minutes.

Energy per unit area, or energy flux, is the product of power per unitarea or, in the case of radiant flux, at the target, and the time ofexposure. Accordingly, the amount of energy per unit area delivered tothe target (for example, in one embodiment, the biological fluid) willvary with the duration of exposure and the irradiance—the radiant powerper unit area incident on the target. In one embodiment the totalradiant energy flux delivered may be between approximately 1–100 J/cm2measured across a wavelength range of between approximately 400–700 nm.In another embodiment, where the light source provides light generallyin the ultraviolet range, the total radiant energy flux delivered to thebiological fluid may preferably be between 1–20 Joules/cm² measuredacross a wavelength range of between approximately 320–400 nm. In onespecific embodiment, the total radiant energy flux delivered to bloodplatelets or blood plasma may be between approximately 1–5 J/cm2 andmore typically approximately 3–4 J/cm² measured across a wavelengthrange of between approximately 320–400 nm. Preferably, the energy shouldnot be outside the predetermined range in that excess heat generatedwithin fluid treatment chamber 40 is to be avoided. For light treatmentof blood platelets and blood plasma, for example, temperature withinchamber 40 should typically not exceed 37° C. If an external temperaturesensor of the type described above is used, the ambient temperatureshould be between 18°–30° C.

During treatment, tray 90 is preferably agitated at a preset frequency.Of course, the frequency should not be so great so as to harm thebiological fluid or components thereof. Typically, the tray 90 may beagitated between approximately 50–100 cycles/min and for bloodplatelets, more preferably, between approximately 55–80 cycles/perminute. A cycle is defined as one complete back and forth oscillation ofdrawer 80.

Once treatment has been successfully completed, fluid from container 206may be transferred to container 210 by breaking frangible number 230 band opening the flow path between the containers 206 and 210 (FIG. 15).Once inside container 210, the biological fluid is allowed to contactthe adsorbent material for a selected period of time. As noted above, inone embodiment, container 210 may also include time-sensitive tabs 209which change color over time. This way, the operator will know if thecontainer has been in contact with the adsorbent material for theappropriate period of time. The adsorbent material is selected to removeany residual photochemical agent or any by products of the photochemicalprocess that may have been included in the biological fluid. Theadsorbent material may include polystyrene beads or activated charcoalor other adsorbent material. Such materials are described in greaterdetail in International Publication No. WO 96/40857, incorporated byreference herein.

Alternatively, in the disposable processing set 240 shown in FIG. 16,the biological fluid may simply pass-through container 246 withoutresiding for any significant time, within the container. The details ofthe removal process and materials used are described in theabove-identified International Publication No. WO96/40857.

The residence time, if any, of the biological fluid in container 210 (or246) will be anywhere between approximately 30 seconds and 7 days. Inaddition, during contact of the biological fluid with the adsorbentmaterial of container 210, it may be desirable to shake or otherwiseagitate container 210 to ensure maximum contact with the adsorbentmaterial.

Regardless of which disposable set is used, after the required residencetime, if any, the biological fluid may be transferred to container 214(or 248 in FIG. 16) by breaking frangible member 230C where it may bestored prior to transfusion to a recipient. Label 216 (or 249) appliedto storage container 214 (or 248) now carries identifying informationregarding the donor and the fluid. Masked bar codes 224 (or 251)indicate successful treatment of the biological fluid and that noadditional treatment is required. The container may be severed andsealed from the remaining portion of the disposable processing set asgenerally described above.

In addition to the treatment function generally described above, thecontrol system may prompt the operator to perform other functions suchas the maintenance function 336 which may include printing a maintenancelog 338, resetting lamp hours 340 resetting bag marker count 342. Theoperator may also select a system settings function 343 which allows theoperator to set dates, times, languages 344,346,348. Finally, thecontrol system may allow the operator to perform certain containermanagement functions such as transmitting or printing container recordsor overwriting container records 350, 352, 354 as generally depicted inFIG. 22.

Alternatively, the diagnostics function shown in general in FIG. 23 maybe selected. Selecting the diagnostics function allows the instrument toperform system tests 356, device tests 358 or provides the operator witha settings menu 360 to select (or change) system identificationsettings, temperature parameters, shaker parameters, lamp parameters,radiometer parameters, lamp factors and light as generally depicted inFIG. 23.

It will be appreciated that various modifications of the embodiments andmethods described herein are possible in accordance with the scope ofthe present invention which are set forth in the appended claims.

1. A method for providing a substantially pathogen-free biological fluidcomprising: providing a source container of a collected biologicalfluid; providing a sterile disposable fluid processing set comprising atleast a treating container integrally pre-connected to a containerincluding a photochemical agent, wherein said treating container ispre-connected to a container housing an adsorbent material with anopenable flow path therebetween, wherein said container housing saidadsorbent material is integrally preconnected to a storage containerwith an openable flow path therebetween; connecting said sourcecontainer to said container including said photochemical agent in asterile manner; establishing fluid communication between said sourcecontainer and said container including said photochemical agent;transferring said biological fluid from said source container to saidtreating container through said container including said photochemicalagent to combine said photochemical agent with said biological fluid;providing a light source capable of providing light sufficient toactivate said photochemical agent; treating said biological fluid insaid treating container by contacting said biological fluid with lightfrom said light source; opening said flow path between said treatingcontainer and said container housing said adsorbent material; contactingsaid biological fluid with said adsorbent material; passing saidbiological fluid from said container housing said adsorbent materialthrough a filter material located between said adsorbent material andsaid storage container and; collecting said biological fluid in saidstorage container.
 2. The method of claim 1 comprising detaching saidsource container from said treating container after said transferring ofsaid biological fluid from said source container.
 3. The method of claim1 comprising detaching said source container and said container thatincluded said photochemical agent from the remainder of said disposableprocessing set after said transferring.
 4. The method of claim 1comprising detaching said treating container from the remainder of saiddisposable processing set.
 5. The method of claim 1 comprisingcontacting said biological fluid with said adsorbent material forbetween approximately 30 seconds and 7 days.
 6. The method of claim 1comprising detaching said container housing said adsorbent material fromsaid storage container.
 7. The method of claim 1 further comprisingexpressing air from said storage container after said collecting step.8. The method of claim 1 comprising indicating on said storage containerthe status of said treatment of fluid.
 9. The method of claim 1comprising agitating said container with said adsorbent materialdisposed therein during said contacting step.
 10. The method of claim 1further comprising: providing a holder for at least said containerhousing said adsorbent material; holding said container housing saidabsorbent material with or within said holder during said treating stepwhile maintaining integral connection with said treating container. 11.The method of claim 10 comprising: holding said storage container withor within said holder during said treating step while maintainingintegral connection with said treating container.
 12. The method ofclaim 1 wherein said contacting step comprises contacting saidbiological fluid with a particulate adsorbent material.